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JACC. Heart Failure Jun 2024Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy.
OBJECTIVES
The aim of this study was to investigate the reported prevalence of pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy-associated genes in patients with acute myocarditis.
METHODS
For this systematic review and meta-analysis, the PubMed and Embase databases were searched on March 4, 2023. Observational studies evaluating the prevalence of P/LP variants in cardiomyopathy-associated genes in patients with acute myocarditis were included. Studies were stratified into adult and pediatric age groups and for the following scenarios: 1) complicated myocarditis (ie, presenting with acute heart failure, reduced left ventricular ejection fraction, or life-threatening ventricular arrhythmias); and 2) uncomplicated myocarditis. The study was registered with the International Prospective Register of Systematic Reviews (CRD42023408668) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Of 732 studies identified, 8 met the inclusion criteria, providing data for 586 patients with acute myocarditis. A total of 89 P/LP variants in cardiomyopathy-associated genes were reported in 85 patients. For uncomplicated myocarditis, the pooled prevalence was 4.2% (95% CI: 1.8%-7.4%; I = 1.4%), whereas for complicated myocarditis, the pooled prevalence was 21.9% (95% CI: 14.3%-30.5%; I = 38.8%) and 44.5% (95% CI: 22.7%-67.4%; I = 52.8%) in adults and children, respectively. P/LP variants in desmosomal genes were predominant in uncomplicated myocarditis (64%), whereas sarcomeric gene variants were more prevalent in complicated myocarditis (58% in adults and 71% in children).
CONCLUSIONS
Genetic variants are present in a large proportion of patients with acute myocarditis. The prevalence of genetic variants and the genes involved vary according to age and clinical presentation.
Topics: Humans; Myocarditis; Acute Disease; Prevalence; Cardiomyopathies
PubMed: 38573261
DOI: 10.1016/j.jchf.2024.02.012 -
European Journal of Neurology Jul 2024This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
Beyond T cell toxicity - Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: A two-case series and literature review.
BACKGROUND AND PURPOSE
This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
METHODS
A systematic literature review was made, with case observations of a melanoma and a non-small cell lung cancer (NSCLC) patient who developed ICI-associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.
RESULTS
Two patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c-LETM), respectively. Intrathecal inflammation with chemokine C-X-C motif ligand (CXCL13) elevation was present in both patients; the triple M case had acetylcholine receptor antibodies, antititin reactivity, altered CD4/CD8 T cell ratio in blood, and depressed programmed death-1 (PD-1) expression on CSF T cells; the c-LETM case showed intrathecal antibody production and plasma cells. Both patients insufficiently responded to first-line treatment. The NSCLC case improved upon administration of B cell-depleting therapy with rituximab, whereas the melanoma patient died before escalation therapy was initiated. Literature research revealed one additional ICI-associated LETM case with intrathecal CXCL13 elevation, three cases with ICI-associated aquaporin-4 antibody neuromyelitis spectrum disorder, and evidence of B cell-mediated toxicity based on antibody-mediated immune pathologies in ICI-associated immune-related adverse events.
CONCLUSIONS
The case observations highlight the plethora of uncertainties in diagnosis and treatment of ICI-associated nirAE, exemplify the heterogeneity of immune mechanisms involved, and suggest a role of B cells, which may be underdiagnosed. Intrathecal CXCL13 may serve as a biomarker of B cell involvement in nirAE, supported by intrathecal immunoglobulin synthesis, presence of plasma cells, and/or recruitment of cognate immune cells.
Topics: Aged; Female; Humans; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Chemokine CXCL13; Immune Checkpoint Inhibitors; Ipilimumab; Lung Neoplasms; Melanoma; Myelitis, Transverse; Nivolumab; T-Lymphocytes
PubMed: 38556899
DOI: 10.1111/ene.16279 -
Cureus Feb 2024This systematic review aimed to look at the effectiveness of venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy in treating fulminant myocarditis and... (Review)
Review
This systematic review aimed to look at the effectiveness of venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy in treating fulminant myocarditis and evaluating the optimal length of time a patient should be placed on VA-ECMO. Fulminant myocarditis is a potentially life-threatening medical condition most commonly brought on by cardiogenic shock, which often progresses to severe circulatory compromise, requiring the patient to be placed on some form of mechanical circulatory assistance to maintain adequate tissue perfusion. Medical centers have multiple mechanical assistive devices available for treatment at their disposal, but our area of focus was placed on one system in particular: VA-ECMO therapy. Although the technology has been around for more than 30 years, there is limited information on how effective VA-ECMO is regarding the treatment of fulminant myocarditis. Due to the lack of data regarding the treatment administration of VA-ECMO for fulminant myocarditis, standard treatment duration guidelines do not exist, resulting in a wide variation of treatment administrations among medical centers. In regard to short-term outcomes, VA-ECMO has shown to be effective in treating fulminant myocarditis, with a one-year post-hospital survival rate ranging from 57.1% to 78% at discharge. For long-term health and survival, the studies that recorded long-term survival ranged from 65% to 94.1%. However, given the small number of studies that pursue this, more research is needed to prove the efficacy of VA-ECMO for the treatment of fulminant myocarditis.
PubMed: 38524063
DOI: 10.7759/cureus.54711 -
Artificial Organs May 2024The Berlin Heart EXCOR® (BHE) can bridge children with severe heart failure to transplantation, but some are successfully weaned and spared transplantation. This study... (Review)
Review
BACKGROUND
The Berlin Heart EXCOR® (BHE) can bridge children with severe heart failure to transplantation, but some are successfully weaned and spared transplantation. This study seeks to identify characteristics of children amenable to successful explantation with BHE support.
METHODS
Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines were used. Five databases were screened for original, English articles measuring BHE support in patients <18 years old based on title and abstract. Exclusion criteria were applied: full-text availability, <10 total pediatric BHE patients, zero successful explantations from BHE, nonprimary literature, adult and pediatric results that could not be separated, and studies with overlapping patient information. Studies were analyzed with descriptive statistics.
RESULTS
From 41 857 potential studies, 14 were analyzed with data from 58 hospitals on four continents from 1990 to 2020. There were 984 BHE patients. The most common diagnosis was dilated cardiomyopathy (n = 318, 32.3%), followed by congenital heart disease (n = 249, 25.3%). There were 85 (8.6%) children explanted with favorable outcomes. The underlying diagnosis was known in 44 (51.8%) cases: 14 (8.4%) of 166 cardiomyopathies, 17 (48.6%) of 35 myocarditis, and 12 (16.7%) of 72 with congenital heart disease were explanted. When the type of support was known, the rate of LVAD patients explanted was 21.3% (n = 19/89) and 2.4% (n = 1/42) of BiVAD patients were explanted.
CONCLUSION
Explantation from BHE is not uncommon at 8.6%, but significant variation exists in the explantation data reported. Myocarditis and LVAD support may be populations suitable for weaning. Standardization of reporting measures and prospective registries may help identify patients suitable for this alternative to transplant and help develop weaning protocols.
Topics: Humans; Child; Adolescent; Heart Transplantation; Heart Failure; Prospective Studies; Heart-Assist Devices; Myocarditis; Treatment Outcome; Heart Defects, Congenital; Retrospective Studies
PubMed: 38419587
DOI: 10.1111/aor.14727 -
European Journal of Clinical... May 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study was to assess the comparative safety profile (odds ratio) of ICIs and estimate the absolute rate of immune-related serious adverse events (irSAEs) in cancer patients undergoing treatment with ICIs.
METHODS
We searched for randomized trials till February 2021, including all ICIs for all cancers. Primary outcome was overall irSAEs, and secondary outcomes were pneumonitis, colitis, hepatitis, hypophysitis, myocarditis, nephritis, and pancreatitis. We conducted Bayesian network meta-analyses, estimated absolute rates and ranked treatments according to the surface under the cumulative ranking curve (SUCRA).
RESULTS
We included 96 trials (52,811 participants, median age 62 years). Risk of bias was high in most trials. Most cancers were non-small cell lung cancer (28 trials) and melanoma (15 trials). The worst-ranked ICI was ipilimumab (SUCRA 14%; event rate 848/10,000 patients) while the best-ranked ICI was atezolizumab (SUCRA 82%; event rate 119/10,000 patients).
CONCLUSION
Each ICI showed a unique safety profile, with certain events more frequently observed with specific ICIs, which should be considered when managing cancer patients.
Topics: Humans; Middle Aged; Immune Checkpoint Inhibitors; Network Meta-Analysis; Carcinoma, Non-Small-Cell Lung; Bayes Theorem; Lung Neoplasms
PubMed: 38372756
DOI: 10.1007/s00228-024-03647-z -
Echocardiography (Mount Kisco, N.Y.) Feb 2024Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations.
METHODS
A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD).
RESULTS
Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF.
CONCLUSIONS
LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population.
HIGHTLIGHTS
What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.
Topics: Adult; Humans; Myocarditis; Echocardiography; Ventricular Function, Left; Stroke Volume; Heart Ventricles; Ventricular Dysfunction, Left
PubMed: 38345413
DOI: 10.1111/echo.15760 -
Frontiers in Immunology 2024The objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors. (Meta-Analysis)
Meta-Analysis
PURPOSE
The objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors.
METHODS
A literature search was performed following the participants, interventions, comparisons, outcomes, and study design (PICOS) principles, and the study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was conducted using Review Manager version 5.4.
RESULTS
This meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on the treatment regimens: PD-1/PD-L1 + chemotherapy versus chemotherapy, PD-1/PD-L1 versus chemotherapy, PD-1/PD-L1 versus placebo, PD-1/PD-L1 + CTLA-4 versus PD-1/PD-L1 and PD-1/PD-L1 + CTLA-4 versus chemotherapy. Compared to chemotherapy treatment alone, PD-1/PD-L1 +chemotherapy significantly increased the risk of hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p = 0.01); grade 3-5 (OR = 1.36, 95% CI [1.04, 1.79], p = 0.03)], hypotension [all-grade (OR = 2.03, 95% CI [1.19, 3.45], p = 0.009); grade 3-5 (OR = 3.60, 95% CI [1.22, 10.60], p = 0.02)], arrhythmia [all-grade (OR = 1.53, 95% CI [1.02, 2.30], p = 0.04); grade 3-5 (OR = 2.91, 95% CI [1.33, 6.39], p = 0.008)] and myocarditis [all-grade (OR = 2.42, 95% CI [1.06, 5.54], p = 0.04)]. The risk of all-grade hypotension (OR = 2.87, 95% CI [1.26, 6.55], p = 0.01) and all-grade arrhythmia (OR = 2.03, 95% CI [1.13, 3.64], p = 0.02) significantly increased when treated with PD-1/PD-L1 inhibitors compared to the placebo. The risks of cardiovascular toxicities are significantly higher with PD-1+CTLA-4 compared to PD-1 alone (OR = 2.02, 95% CI [1.12, 3.66], p = 0.02).
CONCLUSION
PD-1/PD-L1 inhibitor leads to an increased risk of cardiovascular toxicities, especially hypertension, hypotension, arrhythmia, and myocarditis.
Topics: Humans; Arrhythmias, Cardiac; B7-H1 Antigen; CTLA-4 Antigen; Hypertension; Hypotension; Immune Checkpoint Inhibitors; Myocarditis; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 38318172
DOI: 10.3389/fimmu.2024.1255825 -
International Journal of Molecular... Jan 2024The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the...
The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.
Topics: Child; Humans; Aging; Apoptosis; Cardiovascular Diseases; Cell Cycle; MicroRNAs
PubMed: 38256030
DOI: 10.3390/ijms25020956 -
CNS Drugs Feb 2024Despite the evidence that no other antipsychotic is effective as clozapine for the treatment of resistant schizophrenia, it is associated with various metabolic,...
BACKGROUND AND OBJECTIVES
Despite the evidence that no other antipsychotic is effective as clozapine for the treatment of resistant schizophrenia, it is associated with various metabolic, neuroendocrine, cardiovascular, and gastrointestinal adverse effects. Guidelines aiming to address the monitoring of clozapine's (serious) adverse effects can be helpful to prevent and treat these effects. However, many of these guidelines seem to lack one or more important monitoring recommendations. We aimed to systematically review the content and quality of existing monitoring guidelines/recommendations for clozapine-induced adverse effects.
METHODS
A comprehensive and systematic literature search, using the MEDLINE, Embase, Web of Science, and Cochrane databases, was conducted for guidelines/recommendations on the monitoring of clozapine-induced adverse events, published between January 2004 and April 2023 (last search 16 April 2023). Only peer-reviewed published guidelines reporting on the comprehensive monitoring of all major clozapine-induced adverse effects and including evidence-based recommendations, developed after the year 2004, were included. Studies reporting on the monitoring of adverse effects of clozapine without being a formal guideline, guidelines reporting on the monitoring of one or a limited number of adverse effects of clozapine, guidelines that were not peer reviewed or published, expert opinion papers without formal consensus guideline development, or guidelines developed before the year 2004, were excluded. The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool was used to evaluate the guidelines/recommendations' quality.
RESULTS
Only one guideline met the inclusion criteria. This consensus statement made recommendations for hematological monitoring, and the monitoring of metabolic, cardiac, and three other adverse effects. Highest scores for the qualitative assessment were found for the domains "scope and purpose" (66.7%), "clarity of presentation" (44.4%), and "editorial independence" (66.7%). Lowest scores were found for "rigor of development" (14.6%) and "applicability" (0%).
CONCLUSIONS
Future guidelines should develop more comprehensive recommendations about specific clozapine-induced adverse effects, including constipation, myocarditis, tachycardia, and seizures, as well as include a rechallenge policy. There is an urgent need for well-developed, methodologically stringent, guidelines.
REGISTRATION
PROSPERO registration number, CRD42023402480.
Topics: Humans; Clozapine; Antipsychotic Agents; Myocarditis; Schizophrenia; Drug-Related Side Effects and Adverse Reactions
PubMed: 38236524
DOI: 10.1007/s40263-023-01054-z -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409